Central adiponectin acutely improves glucose tolerance in male mice

Endocrinology. 2014 May;155(5):1806-16. doi: 10.1210/en.2013-1734. Epub 2014 Feb 24.


Adiponectin, an adipocyte-derived hormone, regulates glucose and lipid metabolism. It is also antiinflammatory. During obesity, adiponectin levels and sensitivity are reduced. Whereas the action of adiponectin in the periphery is well established the neuroendocrine role of adiponectin is largely unknown. To address this we analyzed the expression of adiponectin and the 2 adiponectin receptors (AdipoR1 and AdipoR2) in response to fasting and to diet-induced and genetic obesity. We also investigated the acute impact of adiponectin on central regulation of glucose homeostasis. Adiponectin (1 μg) was injected intracerebroventricularly (ICV), and glucose tolerance tests were performed in dietary and genetic obese mice. Finally, the influence of ICV adiponectin administration on central signaling cascades regulating glucose homeostasis and on markers of hypothalamic inflammation was assessed. Gene expression of adiponectin was down-regulated whereas AdipoR1 was up-regulated in the arcuate nucleus of fasted mice. High-fat (HF) feeding increased AdipoR1 and AdipoR2 gene expression in this region. In mice on a HF diet and in leptin-deficient mice acute ICV adiponectin improved glucose tolerance 60 minutes after injection, whereas normoglycemia in control mice was unaffected. ICV adiponectin increased pAKT, decreased phospho-AMP-activated protein kinase, and did not change phospho-signal transducer and activator of transcription 3 immunoreactivity. In HF-fed mice, ICV adiponectin reversed parameters of hypothalamic inflammation and insulin resistance as determined by the number of phospho-glycogen synthase kinase 3 β(Ser9) and phospho-c-Jun N-terminal kinase (Thr183/Tyr185) immunoreactive cells in the arcuate nucleus and ventromedial hypothalamus. This study demonstrates that the insulin-sensitizing properties of adiponectin are at least partially based on a neuroendocrine mechanism that involves centrally synthesized adiponectin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / administration & dosage
  • Adiponectin / adverse effects
  • Adiponectin / antagonists & inhibitors
  • Adiponectin / genetics
  • Adiponectin / metabolism
  • Adiponectin / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / metabolism
  • Arcuate Nucleus of Hypothalamus / pathology
  • Diet, High-Fat / adverse effects
  • Glucose Intolerance / etiology
  • Glucose Intolerance / prevention & control*
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Injections, Intraventricular
  • Insulin Resistance*
  • Leptin / genetics
  • Leptin / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Obese
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / immunology
  • Neurons / metabolism
  • Neurons / pathology
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / pathology
  • Obesity / physiopathology*
  • Receptors, Adiponectin / biosynthesis
  • Receptors, Adiponectin / genetics
  • Receptors, Adiponectin / metabolism
  • Signal Transduction / drug effects
  • Ventromedial Hypothalamic Nucleus / drug effects
  • Ventromedial Hypothalamic Nucleus / immunology
  • Ventromedial Hypothalamic Nucleus / metabolism
  • Ventromedial Hypothalamic Nucleus / pathology


  • Adiponectin
  • Adipoq protein, mouse
  • Anti-Inflammatory Agents, Non-Steroidal
  • Hypoglycemic Agents
  • Leptin
  • Nerve Tissue Proteins
  • Receptors, Adiponectin
  • adiponectin receptor 1, mouse
  • adiponectin receptor 2, mouse